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Published on: June 12, 2019
High cholesterol feeding in C57/Blc6 mice alters expression within the VEGF receptor-ligand family in corporal tissue
Donghua Xie1, Surovi Hazarika1, Amy J Andrich1
1Division of Cardiovascular Medicine and the Department of Medicine, Duke University Medical Center, Durham, NC.
Introduction:
Angiogenesis, the growth and proliferation of blood vessels from existing vascular structures, is mediated by many cytokine growth factors and receptors, among the most important are the vascular endothelial growth factor (VEGF) family.
Aim:
Decreases in VEGF receptor signaling have been linked to abnormalities in vasoreactivity in corporal tissue, but it is unknown if alterations in the VEGF ligands and/or receptors contribute to this process.
Main Outcome Measures:
We sought to determine changes in vasoreactivity and the expression of the family of VEGF ligands and receptors in corporal tissue with cholesterol feeding in C57BL6 mice. Methods. Twenty-four mice (N = 8/group) were fed a normal diet (Group 1) or a 1.25% high cholesterol diet for 4 (Group 2) or 12 (Group 3) weeks. Isometric tension studies were performed on corporal strips and dose response curves were generated to evaluate endothelium-dependent and endothelium-independent vasoreactivities. Levels of VEGF-A, B, C, D, VEGF receptors (VEGFRs) were detected by PCR (polymerase chain reaction) and/or western blot/enzyme-linked immunosorbent assay (ELISA). Endothelial and smooth muscle cell contents were determined by immunohistochemistry.
Results:
At 4 weeks there was a small but significant decrease in endothelium-dependent vasoreactivity. Both mRNA and protein levels of VEGFR-1 were decreased, while VEGF-B was increased in Group 2 vs. Group 1, with no change in VEGF-A or endothelial cell content. By 12 weeks, decreases in both endothelium-dependent and endothelium-independent vasoreactivity were evident with decrease in most VEGF ligands (except VEGF-B), receptors, and receptor signaling.
Conclusions:
Cholesterol feeding in C57BL6 mice results in alterations in the VEGF receptor-ligand family that may initially serve to limit the degree of vascular injury but these adaptations fail with the continuation of cholesterol feeding.
Insights
High cholesterol diets alter vascular endothelial growth factor (VEGF) signaling in mice, initially limiting injury but failing with prolonged feeding. These changes impact vasoreactivity and VEGF receptor-ligand expression.
Area of Science:
- Cardiovascular Biology
- Molecular Medicine
- Vascular Biology
Background:
- Angiogenesis, crucial for blood vessel growth, is regulated by growth factors like the vascular endothelial growth factor (VEGF) family.
- VEGF receptor signaling is vital for vasoreactivity in corporal tissue.
Purpose of the Study:
- To investigate how cholesterol feeding affects vasoreactivity in mice.
- To examine changes in VEGF ligands and receptors in corporal tissue under high-cholesterol conditions.
Main Methods:
- C57BL6 mice were fed normal or high-cholesterol diets for 4 or 12 weeks.
- Vasoreactivity was assessed using isometric tension studies on corporal strips.
- VEGF family members and receptors were quantified using PCR, Western blot, and ELISA.
Main Results:
- After 4 weeks, endothelium-dependent vasoreactivity decreased, with reduced VEGFR-1 and increased VEGF-B.
- By 12 weeks, both endothelium-dependent and independent vasoreactivity declined significantly.
- Most VEGF ligands and receptors showed decreased expression by 12 weeks.
Conclusions:
- Cholesterol feeding induces changes in the VEGF receptor-ligand system in mice.
- These adaptations may initially protect against vascular injury but are not sustained with prolonged high cholesterol intake.
